The aim of this project is to define mechanisms of thrombus formation through the study of platelet interactions with adhesive proteins - in particular, fibrinogen/fibrin, von Willebrand factor and collagen type I - under the influence of shear stress. A distinctive feature of this project is the development and use of experimental models, based on laser confocal microscopy and real-time epifluorescent microscopy, for the quantitative evaluation of thrombus formation under defined conditions of flow. The effect of shear forces on the formation of stable platelet thrombi is being evaluated under hemodynamic conditions that mimic those encountered in different districts of the arterial circulation, in order to define how distinct structures in the adhesive molecules under study, including previously unrecognized domains, mediate platelet deposition and accumulation at sites of vascular injury.